基于网络药理学和分子对接技术分析甲硝唑治疗卵巢癌的作用机制  

Mechanism of metronidazole in the treatment of ovarian cancer was analyzed based on network pharmacology and molecular docking technique

作　　者：许悦 吴楚玲 庄圆[1] 杨华 XU Yue;WU Chuling;ZHUANG Yuan;YANG Hua(不详;Department of Gynecology,the Fifth Affiliated Hospital of Sun Yat-sen University,Guangdong Province,Zhuhai 519000,China)

机构地区：[1]中山大学附属第五医院妇科,广东省珠海市519000 [2]中山大学附属第一医院妇科生殖医学中心,广州市510062

出　　处：《临床合理用药杂志》2024年第23期36-40,47,共6页Chinese Journal of Clinical Rational Drug Use

基　　金：广东省医学科学技术研究基金(A2022317)。

摘　　要：目的基于网络药理学和分子对接技术分析甲硝唑治疗卵巢癌潜在可能性及作用机制。方法通过化学数据库PubChem查找甲硝唑的分子信息和分子结构,通过PharmMapper数据库获得甲硝唑潜在的药效团靶点,通过OMIM、PharmGkb、TTD、GeneCards四大数据库收集卵巢癌相关靶点。运用R语言(4.3.1),最终筛选出甲硝唑与卵巢癌的交集靶点基因。应用String在线平台获得蛋白相互作用(PPI)网络,再通过Cytoscape软件进行拓扑分析,找到核心靶点。利用R(4.3.1)对潜在靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。借助在线数据库GEPIA2深入分析核心靶点在卵巢癌中的表达及预后。利用Autodock Vina软件进行药物与核心靶点的分子对接。结果共筛选出甲硝唑的潜在作用靶点68个,卵巢癌相关作用靶点12255个,其中交集靶点56个,GO分析共富集到309个条目,KEGG分析则富集到24条信号通路,最终确定治疗卵巢癌的核心靶点2个,分别为HSP90AA1和MDH2。通过核心靶点基因表达及预后分析,显示MDH2在治疗中具有关键作用。分子对接显示,MDH2与甲硝唑结合活性强。结论甲硝唑能够通过调控多条信号通路而发挥治疗卵巢癌的作用,MDH2是其治疗卵巢癌的核心与关键靶点。Objective The potential and mechanism of metronidazole in the treatment of ovarian cancer were analyzed based on network pharmacology and molecular docking technique.Methods The molecular information and molecular structure of metronidazole were searched through chemical database PubChem,potential pharmacophore targets of metronidazole were obtained through PharmMapper database,and ovarian cancer related targets were collected through OMIM,PharmGkb,TTD and GeneCards databases.The R Programming Language(4.3.1)was used to finally screen out the intersection target genes of metronidazole and ovarian cancer.The protein-protein interaction(PPI)network was obtained using the String online platform,and topological analysis was carried out by Cytoscape software to find the core target.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R(4.3.1).The expression and prognosis of core targets in ovarian cancer were analyzed with GEPIA2 on online database.The Autodock Vina software was used for molecular docking of drugs and core targets.Results A total of 68 potential targets of metronidazole and 12255 targets related to ovarian cancer were screened,including 56 intersection targets.309 items were enriched by GO analysis and 24 signaling pathways were enriched by KEGG analysis,and 2 core targets for the treatment of ovarian cancer were finally identified,namely HSP90AA1 and MDH2.Through core target gene expression and prognosis analysis,MDH2 has a key role in treatment.Molecular docking showed that MDH2 had strong binding activity with metronidazole.Conclusion Metronidazole can play a role in the treatment of ovarian cancer by regulating multiple signaling pathways,and MDH2 is the core and key target of Metronidazole in the treatment of ovarian cancer.

关 键 词：甲硝唑 卵巢癌 网络药理学 分子对接 MDH2 

分 类 号：R285[医药卫生—中药学]